Elevated IgE antibody production is a hallmark of infection with parasitic helminths, including Schistosoma mansoni (Finkelman, F. D., et al., Immun. Today 12:462-466 (1991)). This IgE response is commonly considered an essential component of the host defense against metazoan parasites (Capron, A. et al., Nature 253:474-475 (1975); Capron, A., et al., Prog. Allergy 31:234-267 (1982); Joseph, M., et al., Nature 303:810-812 (1983)). Numerous studies have supported this hypothesis: B cell depletion prevents development of immunity (Bazin, H., et al., J. Immun. 124:2373-2377 (1980)); effective immunity can be adoptively transferred by IgE antibodies (Capron, A. et al., Ann. Rev. Immun. 3:455-476 (1985); Vignali, D. A. A. et al., Immun. Today 10:410-416 (1989)); IgE can directly mediate resistance through eosinophil, macrophage, and platelet-mediated cytotoxicity (Joseph, M., et al., Nature 303:810-812 (1983); Capron, M. et al., J. Immun. 132:462-468 (1984); Auriault, C. et al., Eur. J. Immun. 14:132-138 (1984)). In addition, recent epidemiological reports demonstrate a correlation between high schistosoma-specific IgE antibody levels and resistance to reinfection (Hagan, P. et al., Nature 349:243-2445 (1991); Rihet, P. et al., Eur. J. Immunol. 21:2679-2686 (1991); Dunne, D. W. et al., Eur. J. Immun. 22:1483-1494 (1992). Most of the studies which have been undertaken to investigate the role of IgE in parasite immunity, have employed systems in which IgE is deficient as a result of genetic mutation(s) or via elimination of the pluripotent lymphokine IL-4.
Surprisingly, the present inventors have discovered that elimination of IgE with an IgE antagonist, as measured by reduction of IgE to an undetectable level in an ELISA assay, resulted in decreased worm burden, decreased egg production, and decreased heptospenomegaly in murine schistosomiasis.
Antagonists of IgE in the form of receptors, anti-IgE antibodies, binding factors, or fragments thereof have been disclosed in the art. U.S. Pat. No. 4,962,035 discloses DNA encoding the alpha-subunit of the mast cell IgE receptor or an IgE binding fragment thereof. Hook et al. (Federation Proceedings Vol. 40, No. 3, Abstract #4177) disclose monoclonal antibodies, of which one type is anti-idiotypic, a second type binds to common IgE determinants, and a third type is directed towards determinants hidden when IgE is on the basophil surface.
U.S. Pat. No. 4,940,782. discloses monoclonal antibodies which react with IgE when it is unbound and thereby inhibit IgE binding to mast cells, and react with IgE when it is bound to the B-cell FcE receptor, but do not bind with IgE when it is bound to the mast cell FcE receptor, nor block the binding of IgE to the B-cell receptor.
U.S. Pat. No. 4,946,788 discloses a purified IgE binding factor and fragments thereof, and monoclonal antibodies which react with IgE binding factor and lymphocyte cellular receptors for IgE, and derivatives thereof.
U.S. Pat. No. 5,091,313 discloses antigenic epitopes associated with the extracellular segment of the domain which anchors immunoglobulins to the B cell membrane. The epitopes recognized are present on IgE-bearing B cells but not basophils or in the secreted, soluble form of IgE. U.S. Pat. No. 5,252,467 discloses a method for producing antibodies specific for such antigenic epitopes. U.S. Pat. No. 5,231,026 discloses DNA encoding murine-human antibodies specific for such antigenic epitopes.
WO 89/06138 discloses unique antigenic determinants of IgE present on IgE bearing B-cells but not basophils. One class of these epitopes is at or near the Fc.epsilon.R binding site on IgE, while another class of associated with the extracellular segment of the domain of .epsilon. chains which anchor IgE to the B cell membrane.
U.S. Pat. No. 4,714,759 discloses an immunotoxin in the form of an antibody or an antibody fragment coupled to a toxin to treat allergy.
Presta et al. (J. Immunol. 151:2623-2632 (1993)) disclose a humanized anti-IgE that prevents the binding of free IgE to Fc.epsilon.RI but does not bind to Fc.epsilon.Ri-bound IgE. Copending WO93/04173 discloses polypeptides which bind differentially to the high- and low-affinity IgE receptors.
Flores-Romo et al. (Science 261:1038-1041 (1993)) disclose inhibition of an in vivo antigen-specific IgE response by antibodies to CD23.
Thus, it is an object of this invention to provide a method for preventing or treating parasitic infection by administering an IgE antagonist to a patient.